Cannabinoids are substances isolated as biologically active components of marijuana, and have an antiemetic effect, an intraocular pressure lowering effect, an anticonvulsant effect, an analgesic effect, an orexigenic effect, a bronchodilator effect, an anti-asthmatic effect, an anti-inflammatory effect, an anti-anxiety effect, a sedative effect, a psychotropic effect and the like.
It is known that there are two subtypes of cannabinoid receptors, type 1 (CB1) receptors [Nature, vol. 346, p. 561 (1990)] and type 2 (CB2) receptors.
The CB1 receptors are distributed predominantly in the central nervous system such as brain, and it has been considered that the central effects of cannabinoids such as sedative effect and psychotropic effect are mediated by CB1 receptors. Further, because it has also been confirmed that the CB1 receptors are distributed in tissues which participate in the nociceptive signal transduction such as the dorsal horn of the spinal cord and the dorsal root ganglion neuron (DRG) [Neuroscience, vol. 92, p. 1171 (1999); Molecular and cellular neurosciences, vol. 15, p. 510 (2000)], it has been considered that the analgesic effects of cannabinoids are mediated by CB1 receptors.
On the other hand, it has been confirmed that the CB2 receptors are distributed in the spleen, lymph nodes, and also white blood cells, B cells, T cells, macrophages, mast cells and the like. Because the CB2 receptors are abundantly distributed mainly in tissues and cells of the immune system including hematopoietic cells, it has been considered that the anti-asthmatic effect and anti-inflammatory effect of cannabinoids are mediated by CB2 receptors [Nature, vol. 365, p. 61 (1993); British Journal of Pharmacology, vol. 139, p. 775 (2003)]. In addition, it has been reported that CB2 receptor-selective agonists show a peripheral analgesic effect [Pain, vol. 93, p. 239 (2001); Proceedings of the National Academy of Science of the United States of America, vol. 102, p. 3093 (2005)] and a central analgesic effect [European Journal of Neuroscience, vol. 17, p. 2750 (2003); European Journal of Neuroscience, vol. 22, p. 371 (2005); European Journal of Neuroscience, vol. 23, p. 1530 (2006)], and it has been revealed that the analgesic effects of cannabinoids are also mediated by CB2 receptors. Further, as CB2 receptor-mediated effects, an antipruritic effect (WO2002/065997, WO2003/035109, WO2003/070277, WO2006/046778), an inhibitory effect on osteoclast proliferation and activity [Proceedings of the National Academy of Science of the United States of America, vol. 103, p. 696 (2006)] and the like have also been reported recently.
As described above, as the elucidation of the function of cannabinoid receptors has been progressing, among the modulators of cannabinoid receptor functions, a medicament which does not have effects mediated by the CB1 receptors, that is, central effects such as sedative effect and psychotropic effect have been expected as an excellent medicament without side effects specific to cannabinoids. That is, a CB2 receptor-selective modulator has been expected to be useful as a therapeutic and/or preventive agent for various diseases associated with CB2 receptors without side effects specific to cannabinoids. In particular, CB2-selective agonists have been expected as, for example, therapeutic and/or preventive agents for pains (such as neuropathic pain, trigeminal neuralgia, diabetic pain, postherpetic neuralgia, neuropathic low back pain, HIV-related pain, fibromyalgia, cancer pain, inflammatory pain, acute pain, chronic pain, postoperative pain, acute pain after tooth extraction, chronic musculoskeletal pain, noxious pain, psychogenic pain, and menstrual pain), migraine, pruritus, inflammation, allergies, immunodeficiency, autoimmune diseases, chronic rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, irritable bowel syndrome, multiple sclerosis, asthma (such as airway inflammatory cell infiltration, airway hyperresponsiveness, bronchoconstriction, and mucus hypersecretion), chronic obstructive lung disease, emphysema, pulmonary fibrosis, coughing, allergic rhinitis, dermatitis, atopic dermatitis, arteriosclerosis, glaucoma, anorexia, osteoporosis, and the like.
As the CB2 receptor modulator, for example, a large number of compounds such as indole derivatives, benzimidazole derivatives, sulfonamide derivatives, thiazine derivatives, pyrimidine derivatives, imine derivatives, and pyridone derivatives (see, for example, Non-patent document 1, Patent documents 1, 2, and 3, etc.). Further, imidazole derivatives having a carbamoyl group at the 4-position are also known (see Patent document 4).
Meanwhile, as imidazopyridine derivatives, imidazo[1,2-a]pyridine derivatives having arylamino at the 7-position (see Patent documents 5, 6, and 7), imidazo[1,2-a]pyridine derivatives having aryl in the 2- or 3-position (see Patent documents 8 and 11), and the like are known. Further, imidazo[1,2-a]pyridine derivatives having aminoalkyl at the 3-position (see Patent documents 9 and 10), imidazo[1,2-a]pyridine derivatives having aralkyl at the 3-position (see Patent documents 12 to 14), and further imidazo[1,2-a]pyridine derivatives having alkyl at the 3-position (see Patent document 15), and the like are known. And imidazo[1,2-a]pyridine derivatives having cycloalkylamino or aralkylamino at the 3-position (see Patent documents 16), and imidazo[1,2-a]pyridine derivatives having aralkyl or aroyl at the 3-position (see Patent documents 17) are known.    Patent document 1: WO 2004/035548    Patent document 2: WO 2006/051704    Patent document 3: WO 2006/046778    Patent document 4: WO 2001/58869    Patent document 5: U.S. Published Unexamined Patent Application No. 030610/2006    Patent document 6: U.S. Published Unexamined Patent Application No. 054701/2005    Patent document 7: U.S. Published Unexamined Patent Application No. 049419/2005    Patent document 8: WO 2002/066478    Patent document 9: U.S. Published Unexamined Patent Application No. 0239822/2005    Patent document 10: U.S. Published Unexamined Patent Application No. 0239823/2005    Patent document 11: WO 2002/066477    Patent document 12: U.S. Pat. No. 5,420,138    Patent document 13: U.S. Pat. No. 5,650,414    Patent document 14: U.S. Pat. No. 5,691,347    Patent document 15: U.S. Published Unexamined Patent Application No. 2006/0281750    Patent document 16: WO 2006/094235    Patent document 17: U.S. Published Unexamined Patent Application No. 0148801/2006    Non-patent document 1: “Expert Opin. Ther. Patents.”, 2004, vol. 14, p. 1435